Effects of adjunctive esketamine on depression in elderly patients undergoing hip fracture surgery: a randomized controlled trial

Background Depression is a prevalent perioperative psychiatric complication among elderly hip fracture patients. Esketamine has rapid and robust antidepressant effects. However, it is unknown whether it can alleviate depressive symptoms in elderly patients who undergo hip fracture surgery. This study aimed to explore whether the adjunctive esketamine in patient-controlled intravenous analgesia (PCIA) could improve depressive symptoms in elderly patients undergoing hip fracture surgery. Methods A single-center, prospective, double-blind and randomized controlled clinical trial was carried out from July 2022 to August 2023 at the Wenzhou People's Hospital among 90 patients, aged >= 65 years with hip fracture undergoing elective surgery. Participants were randomly allocated to either the esketamine group (group S) or the control group (group C). In Group S, patients were administered 0.5 mg/kg of esketamine as a PCIA adjuvant for 48 h, while the control group received saline. The primary outcome was the assessment of depressive symptoms using the Geriatric Depression Scale-15 (GDS-15) on postoperative day 2. The secondary outcomes were assessments of depressive symptoms on postoperative day 7 and postoperative day 30, serum levels of brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine (5-HT), postoperative pain intensity, the number of effective PCIA presses, sufentanil consumption, and adverse events. Results The prevalence and GDS-15 scores of depression were significantly lower in group S on postoperative day 2 (28.6% vs. 53.5%; 3.5 +/- 1.8 vs. 4.3 +/- 1.7, P < 0.05). In group S, the number of effective PCIA presses was significantly lower on postoperative day 2 than that in group C [2(1-4) vs. 1(0-2), P<0.05]. Higher levels of BDNF (23.8 +/- 1.7 ng/mL vs. 25.3 +/- 2.0 ng/mL, P < 0.05) and 5-HT (219.5 +/- 19.5 ng/mL vs. 217.0 +/- 22.2 ng/mL, P < 0.05) in the blood were observed on postoperative day 2 in group S. Conclusion In elderly patients aged >= 65 years undergoing hip fracture surgery, the administration of adjunctive esketamine in PCIA could improve depressive symptoms and increase levels of BDNF and 5-HT in the blood. Trial registration Chinese Clinical Trial Registry, ChiCTR2200061956 (Date: 13/07/2022).